Age sensitivity of the Barnes Maze and the Morris Water Maze: Associations with cerebellar cortical Purkinje neurons

Abstract

The goal of this study was to examine age-related changes in spatial memory and its neurobiological substrates as assessed by the Morris water maze (MWM) and the Barnes maze. The MWM is one of the most widely used tests of spatial memory and numerous studies suggest that spatial memory abilities decline with age. To contrast, very few studies exist comparing different ages of mice in the less stressful Barnes maze, and no systematic life span analysis of performance has been published. As the cerebellum is one brain structure that undergoes a quantifiable change in anatomy across the life span (loss of Purkinje neurons), this study evaluated these behavioral tests in terms of sensitivity to both age-related changes in learning as well as age-related changes in the cerebellar cortex. A total of 65 CB6F1 mice were tested at one of five ages (4, 8, 12, 18, or 25 months) on the MWM and Barnes maze. Deficits in spatial memory acquisition were most apparent in both tasks when comparing a subset of good learning mice. Impairment began at 25 months in the MWM and 18 months in the Barnes maze. In all mice, retention was impaired at 25 months on the Barnes maze, but no clear retention deficits were found in the MWM. Unbiased stereology revealed an age-related loss in cerebellar cortical Purkinje neurons from 12-25 months, whereas hippocampus volume remained stable across the life span. Purkinje neuron number, but not hippocampus volume, was correlated with spatial learning in the Barnes maze, with impaired learning associated with lower neuron numbers. For the MWM, Purkinje neuron number was associated with performance in a subset of good learning animals. Overall, mice that learned the Barnes maze well had more Purkinje neurons than poor learners. Both tests were sensitive to heterogeneity in aging at each age tested. Comparisons of good and poor learners across the life span, as well as correlations between the two tasks and brain measures, suggested that the MWM and Barnes maze may be sensitive to different spatial learning abilities and mechanisms of aging.